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Open AccessFeature PaperArticle

The Activity of KV11.1 Potassium Channel Modulates F-Actin Organization During Cell Migration of Pancreatic Ductal Adenocarcinoma Cells

1
Department of Experimental and Clinical Medicine, University of Florence, Viale GB Morgagni 50, 50134 Florence, Italy
2
Physics of Life Processes, Huygens-Kamerlingh Onnes Laboratory, Leiden University, Niels Bohrweg 2, 2333 CA Leiden, The Netherlands
3
Department of Experimental Biochemical and Clinical Sciences, University of Firenze, Viale GB Morgagni 50, 50134 Firenze, Italy
4
Institut für Physiologie II, Robert-Koch-Str. 27b, D-48149 Münster, Germany
5
Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to the manuscript.
Cancers 2019, 11(2), 135; https://doi.org/10.3390/cancers11020135
Received: 21 December 2018 / Revised: 16 January 2019 / Accepted: 17 January 2019 / Published: 23 January 2019
(This article belongs to the Special Issue Ion Channels in Cancer)
Cell migration exerts a pivotal role in tumor progression, underlying cell invasion and metastatic spread. The cell migratory program requires f-actin re-organization, generally coordinated with the assembly of focal adhesions. Ion channels are emerging actors in regulating cell migration, through different mechanisms. We studied the role of the voltage dependent potassium channel KV11.1 on cell migration of pancreatic ductal adenocarcinoma (PDAC) cells, focusing on its effects on f-actin organization and dynamics. Cells were cultured either on fibronectin (FN) or on a desmoplastic matrix (DM) with the addition of a conditioned medium produced by pancreatic stellate cells (PSC) maintained in hypoxia (Hypo-PSC-CM), to better mimic the PDAC microenvironment. KV11.1 was essential to maintain stress fibers in a less organized arrangement in cells cultured on FN. When PDAC cells were cultured on DM plus Hypo-PSC-CM, KV11.1 activity determined the organization of cortical f-actin into sparse and long filopodia, and allowed f-actin polymerization at a high speed. In both conditions, blocking KV11.1 impaired PDAC cell migration, and, on cells cultured onto FN, the effect was accompanied by a decrease of basal intracellular Ca2+ concentration. We conclude that KV11.1 is implicated in sustaining pro-metastatic signals in pancreatic cancer, through a reorganization of f-actin in stress fibers and a modulation of filopodia formation and dynamics. View Full-Text
Keywords: pancreatic cancer; hERG1; fibronectin; desmoplastic matrix; hypoxia; focal adhesions; stress fibers; filopodia; integrins; intracellular Ca2+ concentration pancreatic cancer; hERG1; fibronectin; desmoplastic matrix; hypoxia; focal adhesions; stress fibers; filopodia; integrins; intracellular Ca2+ concentration
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Manoli, S.; Coppola, S.; Duranti, C.; Lulli, M.; Magni, L.; Kuppalu, N.; Nielsen, N.; Schmidt, T.; Schwab, A.; Becchetti, A.; Arcangeli, A. The Activity of KV11.1 Potassium Channel Modulates F-Actin Organization During Cell Migration of Pancreatic Ductal Adenocarcinoma Cells. Cancers 2019, 11, 135.

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